Vascular calcification (VC) is a growing burden in aging societies worldwide, and with a significant increase in all-cause mortality and atherosclerotic plaque rupture, it is frequently found in patients with aging, diabetes, atherosclerosis, or chronic kidney disease. However, the mechanism of VC is still not yet fully understood, and there are still no effective therapies for VC. Regarding energy metabolism factories, mitochondria play a crucial role in maintaining vascular physiology. Discoveries in past decades signifying the role of mitochondrial homeostasis in normal physiology and pathological conditions led to tremendous advances in the field of VC. Therapies targeting basic mitochondrial processes, such as energy metabolism, damage in mitochondrial DNA, or free-radical generation, hold great promise. The remarkably unexplored field of the mitochondrial process has the potential to shed light on several VC-related diseases. This review focuses on current knowledge of mitochondrial dysfunction, dynamics anomalies, oxidative stress, and how it may relate to VC onset and progression and discusses the main challenges and prerequisites for their therapeutic applications.

Insights Into the Role of Mitochondria in Vascular Calcification

Background and Objectives: Vitamin D (Vit D) deficiency has been implicated in various conditions, including cardiovascular disease. The purpose of this retrospective study was to investigate the incidence of patients with myocardial ischemia in relation to their serum levels of vitamin D. Materials and Methods: A 64-month search (January 2016 to April 2021) in our database of the Nuclear Medicine Laboratory revealed 113 patients who had both myocardial perfusion imaging with single photon emission computed tomography (MPI SPECT) and Vit D measurements. MPI SPECT obtained myocardial images during both stress (summed stress score, SSS) and rest (summed rest score, SRS). Abnormal MPI SPECT was when the SSS was ≥4. Vit D was determined by radioimmunoassay (RIA). Patients with Vit D values <10 ng/mL, 10–29 ng/mL and ≥30 ng/mL were defined as having a deficiency, insufficiency and sufficiency, respectively. Results: Among patients, 46/113 (40.7%) were male and 67/113 (59.3%) were female. Abnormal MPI was found in 58/113 (51.3%) patients. Vit D deficiency was noted in 20/113 (17.7%) patients, insufficiency in 86/113 (76.1%) patients, and normal Vit D was noted in only 7/113 (6.2%) patients. Sixteen of the 20 patients (80%) with Vit D deficiency, and 38/86 (44.2%) with insufficiency had an abnormal MPI SPECT. In contrast, only 1/7 (14.3%) patients with sufficient Vit D levels had an abnormal MPI SPECT. The Mann-Whitney U-test showed that ischemia reduced the values of Vit D. Correlation analysis showed a negative association of Vit D levels with SSS (rho = −0.232, p = 0.014) and SRS (rho = −0.250, p = 0.008). Further evaluation with a Vit D cut off 20 ng/mL retrieved no statistical significance. Finally, Vit D and gender were independently associated with myocardial ischemia. Conclusions: Low Vit D levels may represent a risk factor for myocardial ischemia.

https://www.mdpi.com/1648-9144/57/8/774/pdf

Vitamin D Deficiency as a Risk Factor for Myocardial Ischemia.

Aging is a complex process and a significant risk factor for chronic diseases. Menopause, a component of aging in women, is associated with several important cardiometabolic conditions including metabolic syndrome, osteoporosis, and cardiovascular diseases. Menopausal women could benefit from preventative strategies that may decrease morbidity and mortality and improve their quality of life. Vitamins D and K are essential nutrients required for bone health, immune function, and reducing cardiovascular risks, yet their synergistic effect is less understood in aging women. This is the first comprehensive review to summarize the evidence found in randomized clinical trials of the beneficial effects of vitamin D and K co-treatment in postmenopausal women. In our literature search across key electronic databases such as Cochrane, PubMed, and Ovid, we identified 31 pertinent studies. Overall, significant findings indicate that the combined intake of vitamins D and K may positively affect cardiovascular and bone health in postmenopausal women, emphasizing the importance of maintaining a healthy diet rich in vegetables and fermented dairy products. Given the challenges in obtaining all necessary nutrients solely through the diet, vitamin D and K supplements are recommended for postmenopausal women to promote healthy aging and well-being. 

Investigating the Effects and Mechanisms of Combined Vitamin D and K Supplementation in Postmenopausal Women: An Up-to-Date Comprehensive Review of Clinical Studies

Background: The identification of genetic factors that are simultaneously responsible for the predisposition to the development of cardiovascular diseases (CVD) and osteoporosis (OP) is important for the prevention of both conditions.Aim: The aim of this study is to evaluate three genetic risk scales (GRS) that previously showed an association with bone mineral density (BMD) and fracture risk, as well as to study the associations of these GRS with vascular wall pathology.Materials and methods: 250 female outpatients (aged 45 to 69) were enrolled into a cross-sectional study. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation tonometry. Coronary vessels calcium deposits were registered by multispiral computed tomography (MSCT) using the Agatston calcium index (CI). The BMD of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry. Bone resorption marker type-1 collagen C-terminal telopeptide (CTx) was assessed solid-phase enzyme immunoassay. The genetic study included DNA extraction from whole blood samples. Targeted sequencing was performed on the Nextseq550 sequencer (Illumina, USA). Statistical analysis was carried out using the SAS software package for Windows, version 9.0 (SAS Institute Inc., USA).Results: The chance of detecting low bone mass increased more than 4 times at values of IMT ≥0.9 mm (OR=4.17; 95%CI [1.2–14.4], p<0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p><0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p><0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p><0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p><0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI. Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.>< 0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p< 0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p< 0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p< 0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p<0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.>< 0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.

/pdf/associations-of-bone-mass-and-polygenic-risk-of-osteoporosis-560fdwgd.pdf

Associations of bone mass and polygenic risk of osteoporosis with indicators of arterial wall condition

Polysaccharides from Grifola frondosa(GFP) have gained worldwide attention owing to their promising biological activities and potential health benefits. This study aimed to investigate the effects of GFP on alleviation of osteoporosis in ovariectomized (OVX) mice and examine the underlying mechanism. A mouse model of postmenopausal osteoporosis was established by OVX method, Forty eight C57BL/6 female mice were randomly divided into Normal group, OVX alone (Model group, n = 8), OVX + 10 mg/kg GFP (GFP-L group, n = 8), OVX + 20 mg/kg GFP (GFP-M group, n = 8), OVX + 40 mg/kg GFP (GFP-H group, n = 8), OVX + 10 mg/kg Estradiol valerate (Positive group, n = 8). The results showed that compared with Model group, the concentrations of interleukin (IL)-1β, interleukin (IL)-6 and Tumor necrosis factor-α (TNF-α) were significantly reduced, the activity of superoxide dismutase (SOD) and glutathione (GSH) were significantly increased, the content of myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly reduced, and the proteins levels of PINK1, Parkin, Beclin-1 and LC3-II were significantly decreased in the GFP groups. This study demonstrates that GFP alleviates ovariectomy-induced osteoporosis via reduced secretion of inflammatory cytokines, improvement in the oxidative stress status in the body, and inhibition of the PINK1/Parkin signaling pathway. 

Bone protective effects of the polysaccharides from Grifola frondosa on ovariectomy-induced osteoporosis in mice via inhibiting PINK1/Parkin signaling, oxidative stress and inflammation.

The bone mineral density (BMD) loss is closely related to coronary heart disease (CAD). The BMD measured at different locations differ in BMD values, the risk to CAD, and the capability to identify CAD. An average BMD of the right and left femoral neck being below − 1.70 has the ability to indicate risk of CAD. Previous studies have reported that low bone mineral density (BMD) is closely related to coronary artery disease (CAD); however, it is not clear that the BMD loss at which location to what extent has the greatest effect in identifying risk of CAD. This study aimed to evaluate the ability of different measurement sites of BMD in identifying CAD and analyze the best measurement sites and the optimal cut-off of BMD for CAD. This was a cross-sectional study in which 180 of 817 participants were diagnosed with CAD. All participants in the study were measured by dual-energy X-ray absorptiometry (DEXA) for BMD at 8 locations, and following measurements were derived: the average BMD of lumbar spine (L1–L4), femoral neck (left and right), and total proximal femur (left and right). The association between BMD at different locations and CAD was analyzed using logistic regression. The receiver operating characteristic (ROC) curve was used to select the optimal measurement location and cut-off value of the BMD for identifying CAD. There were significant differences in BMD at 3 different measurement locations. Higher BMD is a protective factor against CAD, which is more pronounced in the femoral neck and total proximal femur (ORs = 0.47 ~ 0.66, P < 0.001) than in the lumbar spine (ORs = 0.74 ~ 0.79, P < 0.001). The optimal site for predicting the risk of CAD by BMD is the femoral neck, with the AUC (area under the ROC curve) is 0.72 (95% CI: 0.67 ~ 0.76) and the cut-off is − 1.70. The BMD below particular cut-off of the femoral neck rather than of the lumbar spine may have certain further research value for revealing the risk of CAD.

https://link.springer.com/content/pdf/10.1007/s11657-021-00940-7.pdf

Associations between bone mineral density in different measurement locations and coronary artery disease: a cross-sectional study.

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Associations between bone mineral density in different measurement locations and coronary artery disease: a cross-sectional study.